The overall objectives of research grant number DA-00326-02 are to: (1) Study the involvement of cholinergic systems in the mechanism of action of drugs of abuse. One of the goals for the current year will be to investigate the effects of delta-9-THC and a number of its metabolites and analogues on the level of acetylcholine in certain portions of mouse and rat brain. (2) Investigate the effects of these cannabinoids on turnover rates of acetylcholine in these areas. The effects of a number of narcotic analgesics, narcotic-antagonist analgesics and pure narcotic antagonists will also be examined on this system. (3) Complete the studies of the effects of delta-9-THC on salivary secretion and the involvement of the cholinergic system in this pharmacological effect of cannabinoids. (4) Continue the investigation of the effects of morphine, other analgesics and the narcotic antagonists on their ability to inhibit the release of acetylcholine at ganglionic synapses. These studies also may be extended to a central nervous system synapse. (5) Follow up the interesting observation that intraventricularly administered acetylcholine produces antinociception in laboratory animals and when administered in this way, resembles perenterally administered morphine.